PMID- 27409167
OWN - NLM
STAT- MEDLINE
DCOM- 20180122
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 31
DP  - 2016 Aug 2
TI  - Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer.
PG  - 50490-50506
LID - 10.18632/oncotarget.10466 [doi]
AB  - Phosphoinositide (PIP) phosphatases such as myotubularins (MTMs) inhibit growth 
      factor receptor signaling. However, the function of myotubularin-related protein 
      7 (MTMR7) in cancer is unknown. We show that MTMR7 protein was down-regulated 
      with increasing tumor grade (G), size (T) and stage (UICC) in patients with 
      colorectal cancer (CRC) (n=1786). The presence of MTMR7 in the stroma correlated 
      with poor prognosis, whereas MTMR7 expression in the tumor was not predictive for 
      patients' survival. Insulin reduced MTMR7 protein levels in human CRC cell lines, 
      and CRC patients with type 2 diabetes mellitus (T2DM) or loss of imprinting (LOI) 
      of insulin-like growth factor 2 (IGF2) had an increased risk for MTMR7 loss. 
      Mechanistically, MTMR7 lowered PIPs and inhibited insulin-mediated AKT-ERK1/2 
      signaling and proliferation in human CRC cell lines. MTMR7 provides a novel link 
      between growth factor signaling and cancer, and may thus constitute a potential 
      marker or drug target for human CRC.
FAU - Weidner, Philip
AU  - Weidner P
AD  - Department of Medicine II, Universitatsmedizin Mannheim, Medical Faculty 
      Mannheim, Heidelberg University, D-68167 Mannheim, Germany.
FAU - Sohn, Michaela
AU  - Sohn M
AD  - Department of Medicine II, Universitatsmedizin Mannheim, Medical Faculty 
      Mannheim, Heidelberg University, D-68167 Mannheim, Germany.
FAU - Gutting, Tobias
AU  - Gutting T
AD  - Department of Medicine II, Universitatsmedizin Mannheim, Medical Faculty 
      Mannheim, Heidelberg University, D-68167 Mannheim, Germany.
FAU - Friedrich, Teresa
AU  - Friedrich T
AD  - Department of Medicine II, Universitatsmedizin Mannheim, Medical Faculty 
      Mannheim, Heidelberg University, D-68167 Mannheim, Germany.
FAU - Gaiser, Timo
AU  - Gaiser T
AD  - Institute of Pathology, Universitatsmedizin Mannheim, Medical Faculty Mannheim, 
      Heidelberg University, D-68167 Mannheim, Germany.
FAU - Magdeburg, Julia
AU  - Magdeburg J
AD  - Department of Surgery, Universitatsmedizin Mannheim, Medical Faculty Mannheim, 
      Heidelberg University, D-68167 Mannheim, Germany.
FAU - Kienle, Peter
AU  - Kienle P
AD  - Department of Surgery, Universitatsmedizin Mannheim, Medical Faculty Mannheim, 
      Heidelberg University, D-68167 Mannheim, Germany.
FAU - Ruh, Hermelindis
AU  - Ruh H
AD  - ABIMAS Research Center, Mannheim University of Applied Sciences, D-68163 
      Mannheim, Germany.
FAU - Hopf, Carsten
AU  - Hopf C
AD  - ABIMAS Research Center, Mannheim University of Applied Sciences, D-68163 
      Mannheim, Germany.
FAU - Behrens, Hans-Michael
AU  - Behrens HM
AD  - Institute of Pathology, Christian Albrecht University, D-24105 Kiel, Germany.
FAU - Rocken, Christoph
AU  - Rocken C
AD  - Institute of Pathology, Christian Albrecht University, D-24105 Kiel, Germany.
FAU - Hanoch, Tamar
AU  - Hanoch T
AD  - Department of Biological Regulation, Weizmann Institute of Science, I-7610001 
      Rehovot, Israel.
FAU - Seger, Rony
AU  - Seger R
AD  - Department of Biological Regulation, Weizmann Institute of Science, I-7610001 
      Rehovot, Israel.
FAU - Ebert, Matthias P A
AU  - Ebert MP
AD  - Department of Medicine II, Universitatsmedizin Mannheim, Medical Faculty 
      Mannheim, Heidelberg University, D-68167 Mannheim, Germany.
FAU - Burgermeister, Elke
AU  - Burgermeister E
AD  - Department of Medicine II, Universitatsmedizin Mannheim, Medical Faculty 
      Mannheim, Heidelberg University, D-68167 Mannheim, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (IGF2 protein, human)
RN  - 0 (Insulin)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - EC 3.1.3.48 (MTMR7 protein, human)
RN  - EC 3.1.3.48 (Mtmr7 protein, mouse)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/genetics/*metabolism
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - Genomic Imprinting
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin-Like Growth Factor II/genetics
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Protein Tyrosine Phosphatases, Non-Receptor/*genetics/*metabolism
MH  - Signal Transduction
MH  - Tissue Array Analysis
MH  - Tissue Distribution
PMC - PMC5226598
OTO - NOTNLM
OT  - MTMR7
OT  - colorectal cancer
OT  - insulin
OT  - myotubularin
OT  - phosphatase
COIS- The authors have nothing to declare.
EDAT- 2016/07/14 06:00
MHDA- 2018/01/23 06:00
PMCR- 2016/08/02
CRDT- 2016/07/14 06:00
PHST- 2016/01/13 00:00 [received]
PHST- 2016/06/16 00:00 [accepted]
PHST- 2016/07/14 06:00 [pubmed]
PHST- 2018/01/23 06:00 [medline]
PHST- 2016/07/14 06:00 [entrez]
PHST- 2016/08/02 00:00 [pmc-release]
AID - 10466 [pii]
AID - 10.18632/oncotarget.10466 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Aug 2;7(31):50490-50506. doi: 10.18632/oncotarget.10466.